Study of Letrozole With or Without BYL719 or Buparlisib, for the Neoadjuvant Treatment of Postmenopausal Women

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01923168
First received: August 13, 2013
Last updated: September 4, 2014
Last verified: September 2014
  Purpose

The purpose of the study is to determine whether treatment with a PI3K inhibitor plus letrozole leads to an increase in pathologic response compared to treatment with placebo plus letrozole in patients with Breast cancer


Condition Intervention Phase
Breast Cancer
Drug: BYL719
Drug: BKM120
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Phase II Randomized, Double-blind Placebo Controlled, Study of Letrozole With or Without BYL719 or Buparlisib, for the Neoadjuvant Treatment of Postmenopausal Women With Hormone Receptor-positive HER2-negative Breast Cancer

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Pathological Complete Response [ Time Frame: After 24 weeks of treatment ] [ Designated as safety issue: No ]
    Measure Pathological complete Response after 24 weeks of treatment


Secondary Outcome Measures:
  • Objective response rate according to RECIST 1.1 criteria [ Time Frame: After 24 weeks of treatment ] [ Designated as safety issue: No ]
    Objective response rate according to RECIST 1.1 criteria after 24 weeks of treatment

  • Frequency and severity, of AEs and lab abnormalities [ Time Frame: During 24 weeks of treatment ] [ Designated as safety issue: Yes ]
    To evaluate the safety and tolerability of study treatment based on the frequency, severity AEs, lab abnormalities

  • Rate breast conserving surgery [ Time Frame: After 24 weeks of treatment ] [ Designated as safety issue: No ]
    Rate of breast conserving surgery, following completion of 24 weeks of treatment

  • Molecular markers and correlation with response [ Time Frame: Baseline, Day 15 and 24 weeks of treatment ] [ Designated as safety issue: No ]
    Correlation between pCR and change in Ki67 from baseline to day 15 and baseline to surgery

  • PEPI (preoperative endocrine prognostic index) score [ Time Frame: After 24 weeks of treatment ] [ Designated as safety issue: No ]
    To assess the Preoperative endocrine prognostic index (PEPI) score after 24 weeks of treatment

  • Plasma concentration of BYL719/buparlisib and letrozole when given in combination [ Time Frame: Cycle 1 (Day 1, 2, 8, 15, 22), Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4(Day 1 and Day 2), Cycle 5 Day 1 and Cycle 6 Day 1 ] [ Designated as safety issue: No ]
    Plasma concentration time profiles of BYL719/buparlisib and appropriate individual PK parameters Plasma concentration time profiles of letrozole and appropriate individual PK parameters


Estimated Enrollment: 360
Study Start Date: March 2014
Estimated Study Completion Date: October 2016
Estimated Primary Completion Date: October 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BYL719 + Letrozole
BYL719 + Letrozole in 120 patients
Drug: BYL719
BYL719 + Letrozole
Experimental: Buparlisib + Letrozole
Buparlisib + Letrozole in 120 patients
Drug: BKM120
BKM120 + Letrozole
Placebo Comparator: Placebo + Letrozole
Placebo (of Buparlisib or BYL719 ) with Letrozole in 120 patients
Drug: Placebo
Placebo (of BYL719 or BKM120) + Letrozole

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patient is an adult, female ≥ 18 years old at the time of informed consent
  2. Patient has a histologically and/or cytologically confirmed diagnosis of breast cancer
  3. Patient is postmenopausal.
  4. Patient has T1c-T3, any N, M0, operable breast cancer
  5. Patients must have measurable disease
  6. Patient has diagnostic biopsy available for the analysis of PIK3CA mutation and Ki67 level.
  7. Patient has estrogen-receptor and/or progesterone positive breast cancer as per local laboratory testing
  8. Patient has HER2 negative breast cancer defined as a negative in situ hybridization test or an IHC status of 0 or 1+ as per local laboratory testing

    -

Exclusion Criteria:

  1. Patient has locally recurrent or metastatic disease
  2. Patient has received any systemic therapy (e.g. chemotherapy, targeted therapy, immunotherapy) or radiotherapy for current breast cancer disease before study entry.
  3. Patient with clinically manifest diabetes mellitus (fasting glucose > 120 mg/dl or 6.7 mmol/L), or documented steroid induced diabetes mellitus
  4. Certain scores on an anxiety and depression mood questionnaires
  5. Other protocol-defined inclusion/exclusion criteria may apply

    -

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01923168

Contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682
Contact: Novartis Pharmaceuticals

  Show 99 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01923168     History of Changes
Other Study ID Numbers: CBYL719A2201
Study First Received: August 13, 2013
Last Updated: September 4, 2014
Health Authority: United States: Food and Drug Administration
Australia: Department of Health and Ageing Therapeutic Goods Administration
Austria: Ethikkommission
Belgium: Federal Agency for Medicinal Products and Health Products
Brazil: Ministry of Health
Canada: Health Canada
Colombia: National Institutes of Health
France: Comité consultatif sur le traitement de l'information en matière de recherche dans le domaine de la santé
Germany: German Institute of Medical Documentation and Information
Hong Kong: Department of Health
Italy: The Italian Medicines Agency
Lebanon: Ministry of Public Health
Netherlands: Medicines Evaluation Board (MEB)
Poland: Ministry of Health
South Africa: Medicines Control Council
Spain: Agencia Española de Medicamentos y Productos Sanitarios
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Novartis:
Breast Cancer, Pathological Complete Response, neoadjuvant, hormone receptor-positive

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Letrozole
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Aromatase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 01, 2014